Today about 3.9 billion of the world's population live in areas where there is a risk of dengue transmission. An estimated 100 million dengue infection occur yearly, including 250,000-500,000 severe illness cases and around 25,000 deaths. Dengue is a mosquito-borne viral disease that is caused by transmission of any one of the four dengue virus serotypes (DENV1, DENV2, DENV3, and DENV4). Globally, dengue fever is predominantly spread by two major mosquito vectors: Aedes aegypti (urban-adapted) and Aedes albopictus. The rapid spread of dengue is attributed to urbanization in tropical and subtropical countries, increasing travel within and between endemic countries, and ineffective vector control strategies. Indeed, the disease and economic burden of dengue fever have become a global public health problem.
As so far, no effective antiviral agents are currently available to treat dengue infection and vaccine still in the phase of evaluation. Furthermore, infection with one serotype of dengue virus confers lifelong immunity to the same serotype but increases the risk of developing severe dengue when infected with another serotype. Therefore, the diagnosis of DENY in early stage is very important for disease management. The early diagnosis of dengue virus infection would provide intervention to treat patients and control the epidemics. People infected with the dengue virus exhibit a wide range of clinical presentations, ranging from asymptomatic infections to severe dengue fever, making accurate diagnoses difficult. Current laboratory diagnostic tests for dengue include isolating the virus, viral RNA detection, antigen detection, and serological methods. Virus isolation and viral RNA detection are effective during first five (5) days of illness; both methods can identify the serotype of dengue virus. However, virus isolation is time consuming and viral RNA detection requires special equipment and training personnel. Anti-DENV IgM or IgG antibodies merely appear in blood until 5 days post illness onset and may cross react with other flaviviruses; therefore detection of anti-DENY IgM or IgG is not useful in confirming the presence of the virus during the first 5 days of symptoms and false-positive results could occur frequently.
During the acute phase of the disease (i.e. between days 1 and 7 that follow the onset of illness), dengue virus nonstructural protein 1 (NS1), a 50 kDa glycoprotein, is secreted and accumulate to high concentrations in the blood sera of patients. The presence of NS1 in human sera can be confirmed between 1 and 9 days after infection. In addition, NS1 can be detected when viral RNA is not detectable by RT-PCR and before IgM antibodies appear. NS1 proteins are good target to be an early diagnostic marker. The NS1 antigen detection assays could be performed with simple, low cost, handle large of samples and rapid methods in early diagnosis of DENY. However, although several commercial NS1 detection tests are available to diagnose dengue during the early stages of disease, none of them can differentiate among various dengue serotypes.
There remains a need to develop a diagnostic approach that can detect and differentiate among various dengue serotypes.